Is AD a homogeneous nosologic entity? Yes

Abstract

Alzheimer's disease (AD), the most prevalent disorder causing dementia, is considered a neurodegenerative disease. The cause is unknown for over 95% of the cases who do not have a genetic disease and the pathogenetic mechanisms are incompletely known. The main hypotheses to explain the lesions and the decline in brain functioning are the amyloid cascade and the abnormal phosphorylation of tau protein, which are the grounds for the typical AD lesions: senile plaques and neurofibrillary tangles. Some observations, however, indicate that the relationship between those mechanisms, structural changes, and cognitive state is not univocal or specific. On the other hand, age at onset and clinical presentation are quite variable, as is the duration of the disease. As a matter of fact, a wide differential diagnosis may be necessary and, in the absence of a reliable diagnostic marker, the adscription to widely accepted criteria is compulsory. Nonetheless, the accuracy of the usually applied diagnostic criteria is around 80-90%. From a nosologic perspective, the current clinicopathological concept of AD, with unknown etiology, hypothetically variable pathogenesis, and wide clinical variability, justifies considering AD in a comprehensive manner. Therefore, a disorder primarily affecting structures in medial temporal lobe, with accumulation of amyloid β and abnormal tau, neuritic plaques and tangles, progressive loss of memory and/or other cognitive deficits, ultimately resulting in dementia should be classified as AD. Hopefully, scientific advances (in genetics, proteomics, metabolomics, etc.) will allow a more precise definition of the disease in the future.